GSK's bepirovirsen, the first antisense therapy for chronic hepatitis B, produced a functional cure in about one in five trial participants, and it comes with a boxed warning.
For most people with chronic hepatitis B, treatment is an open-ended commitment: an antiviral pill that keeps the virus suppressed but rarely clears it. On October 20, the US Food and Drug Administration approved a drug built to change that for a subset of patients. Hibsago (bepirovirsen), from GSK, is the first antisense oligonucleotide approved for chronic hepatitis B, and in clinical trials it allowed roughly one in five patients to stop all hepatitis B treatment while keeping the virus in check [1].
Background
Chronic hepatitis B virus (HBV) infection can lead to cirrhosis and raises the risk of liver cancer, according to the FDA [1]. GSK estimates that more than 240 million people live with the infection worldwide, including about 1.7 million in the United States [3]. Standard nucleos(t)ide analogue antivirals suppress the virus but produce a functional cure, meaning no detectable virus or hepatitis B surface antigen (HBsAg) after treatment stops, in only about 1% of patients, according to Ionis Pharmaceuticals, which discovered the drug [7]. As a result, many patients stay on antivirals for years [1].
Bepirovirsen takes a different route. The FDA says it targets the genetic instructions the virus uses to copy itself and make viral proteins, lowering levels of both virus and HBsAg [1]. GSK licensed the drug from Ionis in 2019 [5][7].
What the FDA Approved
The approval covers use alongside existing antiviral therapy in adults without cirrhosis who have taken HBV antivirals for at least six months, have suppressed virus levels, and have HBsAg of 3,000 IU/mL or lower on an FDA-authorized test [1]. The agency also authorized Roche's Elecsys HBsAg II quant II RxDx assay to identify eligible patients [1][4]. The drug received Fast Track, Breakthrough Therapy and Priority Review designations [1].
Hibsago is injected under the skin for up to 24 weeks, reported as 300 mg once weekly, while patients continue their antiviral; they keep taking it for at least 24 weeks after the last injection [1][3][4]. Patients may self-administer after the first dose [4]. Japan approved the drug first, in August 2026 [6].
What the Trials Found
The approval rests on two phase 3, randomized, double-blind, placebo-controlled trials, B-Well 1 and B-Well 2, run in 29 countries [5][7]. B-Well 1 enrolled 981 participants and B-Well 2 enrolled 857; about two-thirds received bepirovirsen on top of antivirals and the rest received placebo plus antivirals [5]. Results were published in the New England Journal of Medicine in May 2026 [2][5].
The primary endpoint was functional cure: undetectable HBV DNA and HBsAg for at least 24 weeks after stopping all treatment [4][7]. In GSK's pooled analysis, 233 of 1,220 bepirovirsen recipients (19%) reached it, compared with 0 of 614 on placebo [3][4]. Rates were 20% in B-Well 1 and 19% in B-Well 2 [3][5]. Among participants with lower baseline HBsAg (1,000 IU/mL or less), 26% (200 of 768) reached functional cure, again versus none on placebo [3][4]. Across both trials, the FDA says 24% of Hibsago recipients met the requirements to stop their existing medicine [1].
For a virus that has spent decades outlasting its treatments, being shown the door by a short strand of synthetic genetic code, even in one patient in five, is a notable plot twist.
Safety and Limitations
Hibsago carries a boxed warning for serious liver reactions and for low platelet counts, which can raise the risk of life-threatening bleeding [1]. Liver enzyme (ALT) elevations of more than 20 to 40 times the upper limit of normal were reported, mostly within the first 12 weeks [4]. The label also warns of worsening kidney function, serious inflammatory reactions such as vasculitis, and risks from improper injection, and regular blood tests are required before and during treatment [1]. The most common side effects were injection-site reactions, fever, fatigue and headache [1][4].
Several caveats apply. About four in five treated participants did not reach functional cure, the comparator was placebo rather than other investigational drugs, and whether functional cure leads to fewer long-term liver complications will take longer follow-up to show [3]. The drug is not approved for people with cirrhosis [1]. The trials' funding and conflict-of-interest statements are not reported here because the full NEJM paper could not be accessed; Ionis is eligible for milestone payments and royalties on sales [7]. Citi analysts called the platelet warning "less expected" while describing both warnings as manageable [6].
Clinical and Patient Implications
For eligible patients, Hibsago offers a fixed course of treatment with a chance, not a guarantee, of coming off antivirals. The FDA's Wendy Carter, DO, acting director of the agency's Office of Infectious Diseases, called it "a new treatment approach" [1]. Practical hurdles remain: an analyst quoted by BioPharma Dive warned that screening, monitoring and clinic capacity could slow uptake [5]. Patients will need to keep their blood-test appointments as faithfully as they once took their pills.
What Comes Next
GSK says it is pursuing approval in other countries, with key decisions expected in the coming months [3]. A price was not disclosed in the reports reviewed for this article [3]. Other candidates aiming for functional cure, including Gilead's selgantolimod, remain in late-stage development [3].
This article is for informational purposes only and is not medical advice; readers should consult their clinician about their own care.
References
US Food and Drug Administration. FDA Approves First-of-Its-Kind Chronic Hepatitis B Treatment. FDA press announcement. October 20, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-its-kind-chronic-hepatitis-b-treatment
Hou J, Lim SG, Buti M, et al. Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection. New England Journal of Medicine. 2026;394(24):2395-2406. DOI: 10.1056/NEJMoa2515131. https://www.nejm.org/doi/full/10.1056/NEJMoa2515131
Pharmaceutical Executive Editorial Staff. FDA Approves Hibsago (Bepirovirsen) for Chronic Hepatitis B. Pharmaceutical Executive. October 21, 2026. https://www.pharmexec.com/view/fda-approves-hibsago-bepirovirsen-chronic-hepatitis-b
Hoffman M. FDA Approves Bepirovirsen, First Antisense Therapy for Chronic Hepatitis B. Contagion Live. October 21, 2026. https://www.contagionlive.com/view/fda-approves-hibsago-first-antisense-therapy-chronic-hepatitis-b
Gardner J. GSK, Ionis unveil data for hepatitis B drug touted as 'functional cure'. BioPharma Dive. May 28, 2026. https://www.biopharmadive.com/news/gsk-ionis-bepirovirsen-hepatitis-b-nejm-study-results/821341/
Barrie R. FDA approves GSK's Hibsago as first functional cure for hepatitis B. Pharmaceutical Technology. October 21, 2026. https://www.pharmaceutical-technology.com/news/fda-approves-gsks-hibsago-as-first-functional-cure-for-hepatitis-b/
Ionis Pharmaceuticals. Ionis partner GSK announces positive topline results from B-Well 1 and B-Well 2 Phase 3 studies for bepirovirsen, a potential first-in-class medicine for chronic hepatitis B. Business Wire / Ionis Investor Relations. January 7, 2026. https://ir.ionis.com/news-releases/news-release-details/ionis-partner-gsk-announces-positive-topline-results-b-well-1